1. Field of the Invention
The instant invention relates to a method for stabilizing a heparin coating to a medical device and more particularly to a method for stabilizing a TDMAC heparin coating to a medical device made of polyvinylchloride (PVC).
2. Description of Related Art
Heparin is a anticoagulant substance which is often applied to the surface of medical devices used in the blood stream to prevent the formation of blood clots. Many medical devices are made of polyvinylchloride (PVC). Heparin may be bound directly to the surface of the PVC device. However, it has been found that heparin has better anti-thrombogenic properties when the heparin molecule is spaced away from the PVC surface. Molecules such as tridodecylmethyl ammonium chloride (TDMAC) and PEO-polyethylene oxide, among others, are used to space the heparin molecule away from the PVC surface and also to bind the heparin molecule to the PVC.
The standard practice for applying TDMAC heparin to a medical device is to first fabricate a medical device made of PVC. The medical device is then dipped in a one to one mixture of toluene/petroleum ether containing a TDMAC heparin complex in, for example, the amount of 1.25-2% by weight for typically about 30 seconds. The coated medical device is then allowed to air dry at room temperature.
The process of binding heparin to TDMAC is believed to be a weak ionic bond. Moreover, the TDMAC material is believed to bind on contact to the PVC material through weak van der Waals bonds. Consequently, it is relatively easy to break the van der Waals bonds thereby removing the TDMAC and its weakly ionic bonded heparin from the medical device.
The PEO-polyethylene oxide molecule bonds to both the heparin and PVC with relatively stronger covalent bonds. As a result, heparin is more strongly bound to PVC with PEO-polyethylene oxide than it is with TDMAC. However, the process of binding the heparin to PVC with PEO-polyethylene oxide is much more complicated than the one step dip process described above to bind heparin to PVC with TDMAC.
Although heparin may be spaced away from and bound to a PVC medical device with TDMAC, when used in the body, the heparin can still be dissolved from the medical device over time. Particularly where the medical device will remain in the patient's body for an extended time, it is desirable to retain the heparin on the medical device for as long as possible in order to minimize the formation of blood clots. In addition, it is preferred that the material binding the heparin to the medical device, in this case TDMAC, not be released into the patient.
Medical devices are also made of polyurethane or silicone. Like PVC, heparin may also be either directly bound or bound through spacer molecules to polyurethane or silicone polymer material. Again, as with medical devices made of PVC, it has been found that heparin has better antithrombogenic properties when the heparin molecule is spaced away from the surface of the polyurethane or silicone.
A disadvantage of using polyurethane or silicone to make medical devices is that polyurethane and silicone are more expensive and difficult to process than PVC. In addition, PVC has additional advantages over polyurethane or silicone. Unlike polyurethane or silicone, PVC is extremely thermosensitive. In particular, PVC can be relatively rigid at room temperature for placement in the patient and then soften dramatically as the medical device warms to body temperatures for increased comfort and reduced trauma to the patient. Further, by varying the percentage of resin to plasticizers, PVC can be made in a variety of stiffnesses to provide a desired balance of physical properties.
An additional benefit to using PVC is that it can be readily compounded with high levels of radiopaque agents making the resulting medical device easily discernible under X-ray or fluoroscopy. In addition, unlike silicone, catheter tips made of PVC can be melt formed to a smooth round shape and tapered tubes., including those with integral connectors, can be easily formed.
In view of the foregoing, it is desirable to strongly bond heparin to PVC through a spacer molecule that is easily applied to the PVC so that medical devices used in the blood stream, particularly devices that will remain in the blood stream for an extended period, may be made of PVC.